Impaired expression of transcription factor IUF1 in a pancreatic beta-cell line derived from a patient with persistent hyperinsulinaemic hypoglycaemia of infancy (nesidioblastosis)

W M Macfarlane, H Cragg, H M Docherty, M L Read, R F James, A Aynsley-Green, K Docherty

    Research output: Contribution to journalArticlepeer-review

    48 Citations (Scopus)

    Abstract

    Persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI), or nesidioblastosis, is a rare disorder which may be familial or sporadic, and which is characterized by unregulated secretion of insulin and profound hypoglycaemia in the neonate. The defect has been linked in some patients to mutations in the sulphonyl urea receptor gene (SUR). The present study investigated potential defects in the regulation of the insulin gene by glucose in a beta-cell line (NES 2Y) derived from a patient with PHHI. The results show that the insulin promoter is unresponsive to glucose in PHHI, and that this defect can be attributed to impaired expression of the transcription factor IUF1. Because IUF1 is involved not only in linking glucose metabolism to the control of the insulin, but is also a major regulator of beta-cell differentiation during embryogenesis, we propose that impaired expression of IUF1 contributes to beta-cell dysfunction in PHHI by leading to abnormal beta-cell differentiation.

    Original languageEnglish
    Pages (from-to)304-8
    Number of pages5
    JournalFEBS Letters
    Volume413
    Issue number2
    Publication statusPublished - 18 Aug 1997

    Keywords

    • Cell Line
    • DNA
    • DNA-Binding Proteins
    • Gene Expression Regulation
    • Glucose
    • Homeodomain Proteins
    • Humans
    • Insulin
    • Islets of Langerhans
    • Pancreatic Diseases
    • Promoter Regions, Genetic
    • RNA, Messenger
    • Recombinant Fusion Proteins
    • Trans-Activators
    • Transcription Factors
    • Transcription, Genetic
    • Upstream Stimulatory Factors

    Fingerprint

    Dive into the research topics of 'Impaired expression of transcription factor IUF1 in a pancreatic beta-cell line derived from a patient with persistent hyperinsulinaemic hypoglycaemia of infancy (nesidioblastosis)'. Together they form a unique fingerprint.

    Cite this